Learning and Memory: Dopamine Drives the Circuit

ReseaRch highlights

Nature Reviews Neuroscience | AOP, published online 11 November 2009; doi:10.1038/nrn2764

LEARNING ANd mEmORy To identify the targets of NPF the authors used different GAL4 lines to drive transcrip- tion of small interfering RNA directed against Dopamine drives the circuit the NPF receptor in different groups of neurons. Only food-deprived flies expressing Flies rely on their sense of smell to navigate the mushroom bodies — specifically, to the the GAL4-c061 driver showed reduced olfac- their environment. Mushroom body neurons vertical and horizontal lobes; this identifies tory memory. The six neurons expressing have a key role in olfactory memory, but little these 12 cells (or a smaller subset of them) GAL4-c061 were found to be dopaminergic is known about the circuits that provide these as the source of the reinforcement signal for and to innervate the mushroom bodies — cells with relevant information. Two studies aversive olfactory conditioning. specifically the medial lobe and peduncle now identify distinct dopaminergic projec- Waddell and colleagues investigated how — indicating that they are a subset of PPL1 tions to specific mushroom body neurons that appetitive olfactory memory retrieval is pro- neurons. Blocking the output of these neu- regulate different aspects of olfactory learning moted by hunger. They used a reinforcement rons improved memory performance in sati- and memory in Drosophila melanogaster. learning paradigm in which flies learned ated flies, whereas activating them inhibited Miesenböck and colleagues used a to associate one of two odours with a sugar memory performance in food-deprived flies. training paradigm in which a fly learned to reward. The flies developed a memory for These findings identify a circuit that regulates associate one of two odours with an electric the conditioned odour, but this memory was memory performance in accordance with shock; as a result, the fly avoided that odour expressed (as a behavioural preference for the a fly’s satiety state: NPF neurons inhibit in subsequent trials. The authors showed odour) only in flies that were starved before dopaminergic PPL1 neurons, thereby remov- that such an olfactory memory could also be testing. So how do states of hunger and satiety ing the inhibitory input to mushroom body induced by pairing exposure to an odour with influence memory performance? neurons and promoting olfactory memory. activation — using an optogenetic activation The authors focused on neuropeptide F These studies point to an olfactory system — of dopaminergic neurons. This (NPF), the D. melanogaster orthologue of memory circuit in D. melanogaster in which suggested that dopamine signalling mediates mammalian neuropeptide Y, which is an dopaminergic PPL1 neurons drive mushroom the storage of aversive odour associations. important regulator of feeding behaviour. body neurons in a manner specific to the Using the same “remote control” to Stimulating NPF neurons in the protocer- stimulus (rewarding or aversive) and the ani- target smaller groups of dopaminergic ebrum (by expressing a heat-sensitive mal’s motivational state (satiated or hungry). neurons revealed that a particular set of four transgene under the control of the transcrip- Leonie Welberg dopaminergic cell clusters was required for tional activator GAL4 driven by the NPF aversive olfactory learning; indeed, blocking promoter and then increasing the ambient ORIGINAL RESEARCH PAPERS Claridge-Chang, A. et al. Writing memories with light-addressable reinforcement activity in these clusters prevented learning. temperature) induced memory retrieval even circuitry. Cell 139, 405–415 (2009) | Krashes, M. J. et al. By labelling the neurons in these clusters in satiated flies. This suggests that satiation A neural circuit mechanism integrating motivational state the authors showed that only the paired prevents memory retrieval by suppressing with memory expression in Drosophila. Cell 139, 416–427 (2009) posterior lateral cluster 1 (PPL1) projects to NPF signalling.

DIGITAL VISION